New genetic circuits created using genes found in Salmonella (Source: MIT)

This circuit allows cells to find the right microenvironment through environmental changes like glucose, pH, temperature and osmolarity

A team of researchers from the Massachusetts Institute of Technology (MIT) has developed the most intricate synthetic biology circuit to date.

Synthetic biology circuits are used to perform functions within cells, such as detecting changing environmental factors like temperature. The problem is that the components in a cell are all mashed together, and creating a complex biological circuit requires that genetic components don't interfere with one another. In other words, researchers don't want proteins that control one part of their synthetic circuit to mess with other parts of the circuit.

To get around this, the team created a synthetic circuit that doesn't interfere with other circuits. They did this by studying the bacterium that causes salmonella, which has a cellular pathway that monitors and controls proteins in human cells. The team then studied 60 other versions of this pathway in other bacteria, and learned that most of the proteins were different enough to not interfere with one another. Clearly, the answer was to expand the number of possible circuits to create components that won't mess with each other.

When expanding the number of circuits, the team then discovered that there was a small amount of "crosstalk" between some circuit components, so this had to be reduced for the complex circuit to work. This was achieved through directed evolution, which is a trial-and-error process that involves the mutation of a gene to create thousands like it and testing them for a desired trait. The best of these genes continue testing until the gene is perfected.

The end result is the most complex synthetic biology circuit that uses four sensors for different molecules. It is layered so that inputs and outputs are proteins that control the next circuit, and they're capable of monitoring the cell's changing environment.

"If a cell needs to find the right microenvironment -- glucose, pH, temperature and osmolarity -- individually they're not very specific, but getting all four of those things really narrows it down," said Christopher Voigt, study author and associate professor of biological engineering at MIT.